C-Type LECTIN receptor-like kinase 1 and ACTIN DEPOLYMERIZING FACTOR 3 are key components of plasmodesmata callose modulation.

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

In-Person or Virtual Educational Preferences in Patients With Fibromyalgia: A Cross-Sectional Survey Study at an Academic Medical Center.

PURPOSE: Patient education is a core component of treating fibromyalgia and central sensitization disorders. We sought to evaluate whether patients with fibromyalgia prefer virtual or in-person educational classes as part of their treatment program, identify underlying factors with their educational modality choice, and highlight benefits or barriers associated with in-person or online educational sessions. DESIGN: A cross-sectional survey with a qualitative feedback component was utilized. METHODS: A voluntary, anonymous survey was distributed to all participants (in-person and virtual) of the fibromyalgia and chronic fatigue clinic treatment program from October 2021 through March 2022. RESULTS: In total 90 participants completed the survey. Nearly all (94%) agreed that the pathophysiologic education was relevant and valuable and (98%) agreed to feeling confident with implementing management strategies. Perceived connection between the participants varied between groups (85% of in-person vs 48% of online; p < .001), as did perceived engagement (100% of in-person vs 71% of online; p = .001). CONCLUSIONS: Patients value education and find it useful in treating fibromyalgia, regardless of the educational modality. The online group reported more limitations including less engagement, class participation, and connection with peers. CLINICAL IMPLICATIONS: As virtual education platforms become more widely available and may be easier to access than in-person options, it is important to understand patient preferences, benefits, and disadvantages of educational modalities to ensure education and patient outcomes remain equitable.

Sialadenoma papilliferum of a minor salivary gland with transformation to mucoepidermoid carcinoma.

Sialadenoma papilliferum (SP) is a rare benign tumor usually occurring in the minor salivary glands. Only two cases of malignant transformation of SP and an occasional case of dysplasia in SP have been reported in the literature till now. We report a case of SP of a minor salivary gland in a middle-aged male where the exophytic component retained the histomorphological features of SP while the endophytic component displayed characteristics of a mucoepidermoid carcinoma. Malignant change in sialadenoma papilliferum is an extremely rare phenomenon that requires further research and documentation. Careful evaluation of morphologic features and reporting of more such cases is required to delineate the clinical behavior of this unusual tumor.

Fibromyalgia Pain and Fatigue Symptoms in Spanish and U.S. Men.

BACKGROUND AND AIMS: Fibromyalgia Syndrome (FMS) is a chronic centralized pain disorder characterized by widespread pain and fatigue. Of those affected by FMS, the majority are women, and minimal research exists involving men. The purpose of this paper is to describe the pain and fatigue experiences of men with FMS from two Western countries, Spain and the United States, in order to support more accurate and earlier recognition and diagnosis in men. DESIGN AND METHODS: We used individual and focus group interviews with qualitative and quantitative assessments. SETTINGS AND PARTICIPANTS/SUBJECTS: Ten men in Spain and seven men in the United States provided information about their symptoms, psychosocial and health-seeking behaviors, and gender experiences with FMS. RESULTS: Men articulated types, trends, and triggers of pain and fatigue that enrich an understanding of their symptoms. For example, men report more localized pain than generalized pain. Employment status and activities, among other contextual factors, impacted men's pain and fatigue experiences. CONCLUSIONS: Men experience distinct facets of pain and fatigue compared with women, with notable similarities and differences across the Spanish and U.S. SAMPLES: Cross-cultural comparisons highlight contextual factors that may inspire future inquiries about determinants of men's experiences with FMS. CLINICAL IMPLICATIONS: The present study could be useful for anyone treating men suffering from FMS, especially care providers in nursing, medical, and psychology fields. These initial findings may prompt a closer examination of recommendations for assessment and diagnostic criteria used internationally for patients with FMS with better recognition of men's experience.

A cross-sectional study of learning styles among continuing medical education participants.

PURPOSE: Experiential learning has been suggested as a framework for planning continuing medical education (CME). We aimed to (1) determine participants' learning styles at traditional CME courses and (2) explore associations between learning styles and participant characteristics. MATERIALS AND METHODS: Cross-sectional study of all participants (n = 393) at two Mayo Clinic CME courses who completed the Kolb Learning Style Inventory and provided demographic data. RESULTS: A total of 393 participants returned 241 surveys (response rate, 61.3%). Among the 143 participants (36.4%) who supplied complete demographic and Kolb data, Kolb learning styles included diverging (45; 31.5%), assimilating (56; 39.2%), converging (8; 5.6%), and accommodating (34; 23.8%). Associations existed between learning style and gender (p = 0.02). For most men, learning styles were diverging (23 of 63; 36.5%) and assimilating (30 of 63; 47.6%); for most women, diverging (22 of 80; 27.5%), assimilating (26 of 80; 32.5%), and accommodating (26 of 80; 32.5%). CONCLUSIONS: Internal medicine and psychiatry CME participants had diverse learning styles. Female participants had more variation in their learning styles than men. Teaching techniques must vary to appeal to all learners. The experiential learning theory sequentially moves a learner from Why? to What? to How? to If? to accommodate learning styles.

Perioperative Cardiovascular Medication Management in Noncardiac Surgery: Common Questions.

Several medications have been used perioperatively in patients undergoing noncardiac surgery in an attempt to improve outcomes. Antiplatelet therapy for primary prevention of cardiovascular events should generally be discontinued seven to 10 days before surgery to avoid increasing the risk of bleeding, unless the risk of a major adverse cardiac event exceeds the risk of bleeding. Antiplatelet therapy for secondary prevention should be continued perioperatively, except before procedures with very high bleeding risk, such as intracranial procedures. Antiplatelet drugs should be continued and surgery delayed, if possible, for at least 14 days after percutaneous coronary intervention without stent placement, 30 days after percutaneous coronary intervention with bare-metal stent placement, and six to 12 months after percutaneous coronary intervention with drug-eluting stent placement. Perioperative beta blockers are recommended for patients already receiving these agents, and it is reasonable to consider starting therapy in patients with known or strongly suspected coronary artery disease or who are at high risk of perioperative cardiac events and are undergoing procedures with a high risk of cardiovascular complications. Long-term statin therapy should be continued perioperatively or started in patients with clinical indications who are not already receiving statins. Clonidine should not be started perioperatively, but long-term clonidine regimens may be continued. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers generally can be continued perioperatively if patients are hemodynamically stable and have good renal function and normal electrolyte levels.

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. METHODS: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). RESULTS: First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. CONCLUSION: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Frequency of Migraine Headaches in Patients With Fibromyalgia.

OBJECTIVE: The purpose of this study was to evaluate the frequency of migraine headache in a large cohort of patients with fibromyalgia using a brief migraine headache-screening tool. BACKGROUND: Several studies report a high prevalence of fibromyalgia among patients with migraine headaches, but there is a dearth of research evaluating the frequency of migraine headaches in patients with fibromyalgia, despite clinical observations suggesting that migraine headaches are common in patients with fibromyalgia. DESIGN AND METHODS: This was a cross-sectional survey study. Patients (N = 3717) with a previous diagnosis of fibromyalgia who were members of the Mayo Clinic Fibromyalgia Registry were contacted by electronic survey and asked to complete a brief demographic and medical history questionnaire and the validated ID-Migraine screener. RESULTS: A total of 1730 patients (46.5%) completed the electronic survey. The majority of participants were white (97.2%), female (92.5%), with a mean age of 56.2 (±13.1) years. Of the respondents, 966 (55.8%) met criteria for migraine headaches. Hypertension (309 [32.3%] vs. 294 [40.1%], P = .004), asthma (312 [32.5%] vs. 189 [25.9%], P = .011), irritable bowel syndrome (520 [54.6%] vs. 348 [47.6], P = .017), chronic fatigue syndrome (486 [50.7%] vs. 271 [37.1], P < .0001), depression (634 [66.5%] vs. 413 [56.7%], P = .0002), anxiety (415 [43.5%] vs. 252 [34.7%], P = .0011), and post-traumatic stress disorder (172 [18.0%] vs. 96 [13.2%], P = .006) were all significantly more common in those who met criteria for migraine headaches than those who did not. CONCLUSION: The results of this study suggest that migraine headaches are common in patients with fibromyalgia. Clinicians who care for either population must be aware that these conditions commonly overlap and can significantly increase a patient's cumulative disease burden.

A Cross-Sectional Survey Study of Cannabis Use for Fibromyalgia Symptom Management.

OBJECTIVE: To assess the use of cannabis as a symptom management strategy for patients with fibromyalgia. PATIENTS AND METHODS: An electronic, cross-sectional survey was conducted among patients diagnosed with fibromyalgia and treated in Integrative Medicine & Health at Mayo Clinic, Rochester, Minnesota. The survey was constructed with the Symptom Management Theory tool and was sent anonymously via web-based software to patients with a diagnosis of fibromyalgia. RESULTS: Of 5234 patients with fibromyalgia sent the online survey, 1336 (25.5%) responded and met the inclusion criteria. Survey respondents had a median age of 48 (Q1-Q3: 37.5-58.0) years, and most identified as female. Nearly half of respondents (49.5%, n=661) reported cannabis use since their fibromyalgia diagnosis. The most common symptoms for which respondents reported using cannabis were pain (98.9%, n=654); fatigue (96.2%; n=636); stress, anxiety, or depression (93.9%; n=621); and insomnia (93.6%; n=619). Improvement in pain symptoms with cannabis use was reported by 82.0% (n=536). Most cannabis-using respondents reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia. CONCLUSION: Considering that cannabis is a popular choice among patients for managing fibromyalgia symptoms, clinicians should have adequate knowledge of cannabis when discussing therapeutic options for fibromyalgia with their patients.

Emotional experiences and gender roles of men with fibromyalgia syndrome: a cross-cultural qualitative study.

Introduction: Gender roles may impact men with fibromyalgia, causing a high number of negative emotional states and affective disorders. There are few studies that detect men's high emotional suffering. This study examined the emotional experience of men with fibromyalgia. Methods: A qualitative cross-cultural study utilized inductive thematic analysis was performed at the Fibromyalgia and Chronic Fatigue Unit Santa Maria University Hospital in Spain, the Fibromyalgia and Chronic Fatigue Clinic at Mayo Clinic in the US, and volunteers from the Winneshiek County in the US A total of 17 participants, 10 men from Spain and 7 men from the US were included. Results: Three themes related to feelings/emotions emerged: (1) psychological level; (2) social level; and (3) physical level. Men with fibromyalgia from Spain and the US experienced many negative emotions. Men often experience negative emotions that are worsened by common misunderstandings and social biases/stigma about their condition. Conclusion/implications: A proper assessment of emotions when evaluating the global health of men with fibromyalgia as well as the provision of emotional support would improve their mental health and therefore their overall physical health. Emotional management should be incorporated into all treatment protocols for fibromyalgia, especially for men given the gender stigma. Health policies designed by legislators, policymakers, and support agencies must be accompanied by education in gender role concepts to improve the emotions of men with FMS. The mass media will be essential for the disclosure of the emotional suffering of male patients so that society might better understand them.

Robotics in Massage: A Systematic Review.

Background: Over the past few years, a growing number of studies have explored massage robots. However, to date, a dedicated systematic review focused solely on robot-assisted massage has not been conducted. Objective: To systematically identify and summarize evidence from studies concerning robot-assisted massage in healthcare settings. Methods: An extensive literature search, involving electronic databases Ovid and Scopus, was conducted from the inception of the databases up to March 2023. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and relevant papers were chosen based on the predefined inclusion criteria. Given the substantial methodological diversity among the included studies, a qualitative analysis was conducted. Results: Seventeen studies met the inclusion criteria, comprising 15 preliminary trials, one quasi-experimental study, and one randomized controlled trial. Approximately 29% of the studies focused on the application of robotic massage for patients, 24% targeted both healthy volunteers and patients, and the remaining 47% were preclinical trials assessing the effectiveness of robotic massage solely on healthy volunteers. Primary interventions included robotic massage for oral rehabilitation, scalp massage, low back massage, shoulder massage, and full-body massage. All studies provided evidence that robotic massage interventions can enhance health and well-being, indicating a promising future for the integration of robotics in the field of massage therapy. Conclusions: In general, robotic massage interventions offer physical and mental health benefits. Robot-assisted massage may be integrated into care provision as an adjunct to enhance human well-being. Nonetheless, further research is needed to confirm these findings.

Central sensitization, chronic pain, and other symptoms: Better understanding, better management.

Central sensitization, a pathophysiologic process in which the central nervous system undergoes changes that alter its processing of pain and other sensory stimuli, may be the mechanism underlying various conditions in which patients have unexplained pain and fatigue. Patients frequently misunderstand the cause of their symptoms and pursue unnecessary evaluations and treatments. Clinicians have a pivotal role in decreasing this misunderstanding by providing patient education, which can affect perception, management, functional status, and quality of life.

Continuing Medical Education in the Post COVID-19 Pandemic Era.

Continuing medical education (CME) is a requirement for medical professionals to stay current in their ever-changing fields. The recent significant changes that have occurred due to the COVID-19 pandemic have significantly impacted the process of providing and obtaining CME. In this paper, an updated approach to successfully creating and administering CME is offered. Recommendations regarding various aspects of CME development are covered, including competitive assessment, marketing, budgeting, property sourcing, program development, and speaker and topic selection. Strategies for traditional and hybrid CME formats are also explored. Readers and institutions interested in developing CME, especially in the setting of the ongoing pandemic, will be able to use these strategies as a solid framework for producing CME. The recommendations and strategies presented within this paper are based on the authors' opinions, expert opinions, and experiences over 13 years of creating CME events and challenges brought about due to the COVID-19 pandemic.

The Safety and Efficacy of Low-Dose Naltrexone in Patients with Fibromyalgia: A Systematic Review.

Fibromyalgia (FM) is a chronic pain sensitivity syndrome characterized by diffuse musculoskeletal pain and many other systemic manifestations. Low-dose naltrexone (LDN) has been increasingly used as an off-label treatment option in FM. However, current evidence on the safety and efficacy of LDN in patients with FM is not well known. To systematically assess the current evidence on the safety and efficacy of LDN use in the treatment of FM. A comprehensive bibliographic search was conducted on EBM Reviews - Cochrane Central Register of Controlled Trials, EBM Reviews - Cochrane Database of Systematic, Embase, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions and Scopus databases in September 2022. Inclusion criteria were articles that were published in English, focusing on clinical trials involving LDN for the treatment of FM. Two reviewers independently screened and extracted the data. A qualitative analysis was used due to the high methodological heterogeneity between studies. The electronic search produced 805 articles. After applying the inclusion criteria, 9 articles (one RCT, two case reports, two case series, and four pilot trials) were selected for evaluation. LDN intervention protocols, study designs, and follow-up periods were different among the included studies. Overall, LDN was found to be effective in the symptomatic management of FM, and of the 78% of included studies that evaluated for safety, no severe adverse events were reported. Proving the efficacy and safety of low-dose naltrexone is a future possibility based on current study data, but the level of scientific evidence is limited. Future well-designed trials with large sample sizes are required.

Clinical outcome measures reporting in randomized trials evaluating Tuina therapy for chronic nonspecific low back pain: A systematic review.

BACKGROUND: Tuina has gained widespread attention and utilization for the management of chronic nonspecific low back pain (CNLBP). However, evidence-based guidance for choosing accurate and appropriate outcome measures of Tuina is lacking. The objective of this study is to systematically synthesize the existing outcome measures reported in randomized controlled trials (RCTs) evaluating Tuina therapy in CNLBP. METHODS: Electronic literature searches were conducted in multiple English and Chinese databases from their inception to May 2022. RCTs were included if they involved clinical outcome measures in Tuina treatment for patients with CNLBP. Outcome instruments for each study were extracted and analyzed. Evidence from included studies were assessed using the Cochrane risk-of-bias tool. RESULTS: Of the 735 identified articles, 17 articles with 1628 participants were included. Measurement domains in these RCTs were mainly reported in terms of pain (94%) and physical activity (71%), followed by safety (41%), Chinese medicine outcome (35%), and quality of life (12%). Moreover, several limitations with existing outcomes were reported, including lack of emphasis on the evaluation of quality of life, inadequate safety monitoring, as well as insufficient and vague Chinese medicine outcome measures. All trials were deemed to be of poor methodological quality. CONCLUSION: Pain and physical disability were the most frequently studied outcome domains in CNLBP treated by Tuina therapy. More rigorous and high-quality trials with appropriately selected outcome measures are needed in the future.

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials.

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review. Design: Systematic review of randomized controlled trials (RCTs). Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies. Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program. Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Implementation of eLearning solutions for patients with chronic pain conditions.

Background: Digital and mobile (mHealth) solutions are online or application-based services intended to support individuals with health needs. Despite evidence supporting the use of mHealth for patients with chronic pain, and the increasing desire of these types of solutions by both patients and providers, adoption of mHealth solutions remains limited. Implementation mapping can serve as a practical method to facilitate implementation and adoption of mHealth solutions within healthcare settings. Methods: Implementation mapping was used to develop implementation strategies based on contextual determinants organized within the Consolidated Framework for Implementation Research (CFIR) for mHealth eLearning solutions across an integrated, multi-site healthcare system. We describe our experience identifying stakeholders, delineating implementation facilitators and barriers, defining implementation outcomes using RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, outlining initial implementation strategies, and iterating on implementation strategies. Results: A total of 30 implementation strategies were identified and implemented. Over the first year, primary and specialty care providers across all the clinical sites (n = 70) placed 2559 orders for the mHealth solution. Most patients reported receiving the mHealth eLearning module (74%), and most patients felt that the tool improved their knowledge regarding their condition (82%) and their ability to provide self-care related to the condition (73%). Conclusion: Practical applications of implementation science methods can help enable change within healthcare settings. Implementation mapping is an exercise that can engage stakeholders to facilitate the incorporation of new methods of care delivery, including mHealth solutions.

Physical Activity and Exercise Experience in Spanish and US Men with Fibromyalgia: A Qualitative Cross-Cultural Study.

Physical exercise is an indispensable element in the multidisciplinary treatment of fibromyalgia syndrome (FMS). The present study examined if men diagnosed with FMS engaged in any type of physical activity or exercise, the perceived effects from exercise, and who specifically recommended exercise. A qualitative cross-cultural study was performed in fibromyalgia clinical units in Spain and the United States. A total of 17 participants, 10 men from Spain and 7 men from the US, were included. In Spain, a focus group was completed in two parts, one month apart in 2018. In the US, five individual interviews and one joint interview with two men were completed in 2018. Three central themes appeared in the qualitative data: (1) Understanding what constitutes physical activity or exercise, (2) Facilitating or discouraging the performance of physical exercise, and (3) Effects of physical activity or exercise on psychological and social symptoms. The actual practice of exercise by patients with FMS is often perceived as leading to pain and fatigue, rather than a treatment facilitator. Physical activity and exercise can provide benefits, including relaxation, socialization, and increased muscle tone. However, minor opioids limit physical activity as they cause addiction, drowsiness, and decrease physical activity in Spanish men. Recommendations in a clinical setting should incorporate exercise as well as physical activity via daily life activities.